Butyricimonas is a key gut microbiome component for predicting postoperative recurrence of esophageal cancer.

BACKGROUND: Recently, intestinal bacteria have attracted attention as factors affecting the prognosis of patients with cancer. However, the intestinal microbiome is composed of several hundred types of bacteria, necessitating the development of an analytical method that can allow the use of this information as a highly accurate biomarker. In this study, we investigated whether the preoperative intestinal bacterial profile in patients with esophageal cancer who underwent surgery after preoperative chemotherapy could be used as a biomarker of postoperative recurrence of esophageal cancer. METHODS: We determined the gut microbiome of the patients using 16S rRNA metagenome sequencing, followed by statistical analysis. Simultaneously, we performed a machine learning analysis using a random forest model with hyperparameter tuning and compared the data obtained. RESULTS: Statistical and machine learning analyses revealed two common bacterial genera, Butyricimonas and Actinomyces, which were abundant in cases with recurrent esophageal cancer. Butyricimonas primarily produces butyrate, whereas Actinomyces are oral bacteria whose function in the gut is unknown. CONCLUSION: Our results indicate that Butyricimonas spp. may be a biomarker of postoperative recurrence of esophageal cancer. Although the extent of the involvement of these bacteria in immune regulation remains unknown, future research should investigate their presence in other pathological conditions. Such research could potentially lead to a better understanding of the immunological impact of these bacteria on patients with cancer and their application as biomarkers.

NLRC4-driven production of IL-1ß discriminates between pathogenic and commensal bacteria and promotes host intestinal defense.

Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we found that intestinal phagocytes were anergic to ligands for Toll-like receptors (TLRs) or commensals but constitutively expressed the precursor to interleukin 1ß (pro-IL-1ß). After infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produced mature IL-1ß through the NLRC4 inflammasome but did not produce tumor necrosis factor (TNF) or IL-6. BALB/c mice deficient in NLRC4 or the IL-1 receptor were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. That enhanced lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment and poor intestinal pathogen clearance. Thus, NLRC4-dependent production of IL-1ß by intestinal phagocytes represents a specific response that discriminates pathogenic bacteria from commensal bacteria and contributes to host defense in the intestine.

Association of temporal change in body mass index with sudden cardiac arrest in diabetes mellitus.

BACKGROUND: Underweight imposes significant burden on cardiovascular outcomes in patients with diabetes mellitus. However, less is known about the impact of serial change in body weight status measured as body mass index (BMI) on the risk of sudden cardiac arrest (SCA). This study investigated the association between SCA and temporal change in BMI among patients with diabetes mellitus. METHODS: Based on Korean National Health Insurance Service database, participants with diabetes mellitus who underwent health examination between 2009 and 2012 and had prior health examination data (four years ago, 2005-2008) were retrospectively analyzed. BMI was measured at baseline (2005-2008) and 4-year follow-up health examination (2009-2012). Patients were classified in four groups according to the body weight status and its temporal change: sustained non-underweight, sustained underweight, previous underweight, and newly developed underweight. Primary outcome was defined as occurrence of SCA. RESULTS: A total of 1,355,746 patients with diabetes mellitus were included for analysis, and SCA occurred in 12,554 cases. SCA was most common in newly developed underweight (incidence rate = 4.45 per 1,000 person-years), followed by sustained underweight (incidence rate = 3.90), previous underweight (incidence rate = 3.03), and sustained non-underweight (incidence rate = 1.34). Adjustment of covariates resulted highest risk of SCA in sustained underweight (adjusted hazard ratio = 2.60, 95% confidence interval [2.25-3.00], sustained non-underweight as a reference), followed by newly developed underweight (2.42, [2.15-2.74]), and previous underweight (2.12, [1.77-2.53]). CONCLUSIONS: In diabetes mellitus, sustained underweight as well as decrease in body weight during 4-year follow-up imposes substantial risk on SCA. Recovery from underweight over time had relatively lower, but yet increased risk of SCA. Both underweight and dynamic decrease in BMI can be associated with increased risk of SCA.

Distinct Commensals Induce Interleukin-1ß via NLRP3 Inflammasome in Inflammatory Monocytes to Promote Intestinal Inflammation in Response to Injury.

The microbiota stimulates inflammation, but the signaling pathways and the members of the microbiota involved remain poorly understood. We found that the microbiota induces interleukin-1ß (IL-1ß) release upon intestinal injury and that this is mediated via the NLRP3 inflammasome. Enterobacteriaceae and in particular the pathobiont Proteus mirabilis, induced robust IL-1ß release that was comparable to that induced by the pathogen Salmonella. Upon epithelial injury, production of IL-1ß in the intestine was largely mediated by intestinal Ly6C(high) monocytes, required chemokine receptor CCR2 and was abolished by deletion of IL-1ß in CCR2(+) blood monocytes. Furthermore, colonization with P. mirabilis promoted intestinal inflammation upon intestinal injury via the production of hemolysin, which required NLRP3 and IL-1 receptor signaling in vivo. Thus, upon intestinal injury, selective members of the microbiota stimulate newly recruited monocytes to induce NLRP3-dependent IL-1ß release, which promotes inflammation in the intestine.

Long-term increase in fasting blood glucose is associated with increased risk of sudden cardiac arrest.

BACKGROUND: Diabetes mellitus (DM) is associated with various cardiovascular complications, including sudden cardiac arrest (SCA). Furthermore, the severity of DM, as assessed by fasting blood glucose (FBG), is associated with the risk of SCA. However, whether long-term changes in FBG influence on SCA risk remains to be determined. METHODS: This study used sequential nationwide health screening data from 2009 and 2011. FBG was measured at each health screening, and ΔFBG was calculated as FBG in 2011-FBG in 2009. RESULTS: Overall, 2,801,153 people were analyzed, and the mean follow-up duration was 6.33 years. Compared with the euglycemic group (- 20 ≤ ΔFBG < 20), the 20 ≤ ΔFBG < 40, 40 ≤ ΔFBG < 100, and ΔFBG ≥ 100 groups had increased SCA risks of 25% (adjusted hazard ratio [HR] = 1.25; 95% confidence interval [CI] 1.16-1.35; p < 0.001), 66% (adjusted HR = 1.66; 95% CI 1.49-1.86; p < 0.001), and 2.9-fold (adjusted HR = 2.85; 95% CI 2.37-3.44; p < 0.001), respectively. The association between ΔFBG and SCA was maintained in people with DM but not in people without DM. However, sex, age, blood pressure, and presence of heart failure did not affect the association between ΔFBG and SCA. A decrease in ΔFBG over time was not associated with reduced risk of SCA: the adjusted HR was 1.11 (95% CI 0.98-1.27; p = 0.113) for the ΔFBG < -40 group and 1.12 (95% CI 1.03-1.22; p = 0.009) for the - 40 ≤ ∆FBG < - 20 group. CONCLUSIONS: A long-term increase in ΔFBG can be associated with increased risk of SCA in people with DM. However, a long-term decrease in ΔFBG was not associated with reduced risk of SCA. Actions to prevent increase in FBG can have significant effects on public health in terms of SCA prevention.

Association between low-density lipoprotein cholesterol and sudden cardiac arrest in people with diabetes mellitus.

BACKGROUND: Dyslipidemia measured as low-density lipoprotein (LDL)-cholesterol is an established risk factor of cardiovascular disease, which is more pronounced in diabetes population. Less is known about the association of LDL-cholesterol level and sudden cardiac arrest (SCA) risk in diabetes mellitus patients. This study investigated the association of LDL-cholesterol level and SCA risk in diabetes population. METHODS: This study was based on Korean National Health Insurance Service database. Patients who received general examination from 2009 to 2012 and diagnosed as type 2 diabetes mellitus were analyzed. Primary outcome was defined as SCA event identified with International Classification of Disease code. RESULTS: A total of 2,602,577 patients were included, with total follow-up duration of 17,851,797 person * year. Mean follow-up duration was 6.86 years, and 26,341 SCA cases were identified. Overall incidence of SCA was highest in the lowest LDL-cholesterol group (< 70 mg/dL) and decreased in a linear manner as LDL-cholesterol rises, till 160 mg/dL. Adjustment of covariates resulted in U-shape association, with highest risk of SCA in the highest LDL-cholesterol group (≥ 160 mg/dL) followed by lowest LDL-cholesterol group (< 70 mg/dL). In subgroup analysis, U-shape association between SCA risk and LDL-cholesterol was more pronounced in male, non-obese people, and those who did not use statins. CONCLUSIONS: In people with diabetes, the association between SCA and LDL-cholesterol level was U-shaped with highest and lowest LDL-cholesterol group having higher risk of SCA than others. Low LDL-cholesterol level can be a surrogate marker for increased risk of SCA in people with diabetes mellitus and this paradoxical association should be recognized and extended to clinical preventive measures.

Identification of concealed cardiomyopathy using next-generation sequencing-based genetic testing in Korean patients initially diagnosed with idiopathic ventricular fibrillation.

AIMS: Idiopathic ventricular fibrillation (IVF) is a disease in which the cause of ventricular fibrillation cannot be identified despite comprehensive clinical evaluation. This study aimed to investigate the clinical yield and implications of genetic testing for IVF. METHODS AND RESULTS: This study was based on the multi-centre inherited arrhythmia syndrome registry in South Korea from 2014 to 2017. Next-generation sequencing-based genetic testing was performed that included 174 genes previously linked to cardiovascular disease. A total of 96 patients were clinically diagnosed with IVF. The mean age of the onset was 41.2 ± 12.7 years, and 79 patients were males (82.3%). Of these, 74 underwent genetic testing and four (5.4%) of the IVF probands had pathogenic or likely pathogenic variants (each having one of MYBPC3, MYH7, DSP, and TNNI3). All pathogenic or likely pathogenic variants were located in genes with definite evidence of a cardiomyopathy phenotype, either hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Next-generation sequencing-based genetic testing identified pathogenic or likely pathogenic variants in 5.4% of patients initially diagnosed with IVF, suggesting that genetic testing with definite evidence genes of cardiomyopathy may enable molecular diagnosis in a minority of patients with IVF. Further clinical evaluation and follow-up of patients with IVF with positive genotypes are needed to unveil concealed phenotypes, such as the pre-clinical phase of cardiomyopathy.

Dysfunction of Foxp3+ Regulatory T Cells Induces Dysbiosis of Gut Microbiota via Aberrant Binding of Immunoglobulins to Microbes in the Intestinal Lumen.

Foxp3+ regulatory T (Treg) cells prevent excessive immune responses against dietary antigens and commensal bacteria in the intestine. Moreover, Treg cells contribute to the establishment of a symbiotic relationship between the host and gut microbes, partly through immunoglobulin A. However, the mechanism by which Treg cell dysfunction disturbs the balanced intestinal microbiota remains unclear. In this study, we used Foxp3 conditional knockout mice to conditionally ablate the Foxp3 gene in adult mice and examine the relationship between Treg cells and intestinal bacterial communities. Deletion of Foxp3 reduced the relative abundance of Clostridia, suggesting that Treg cells have a role in maintaining Treg-inducing microbes. Additionally, the knockout increased the levels of fecal immunoglobulins and immunoglobulin-coated bacteria. This increase was due to immunoglobulin leakage into the gut lumen as a result of loss of mucosal integrity, which is dependent on the gut microbiota. Our findings suggest that Treg cell dysfunction leads to gut dysbiosis via aberrant antibody binding to the intestinal microbes.

Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry.

Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. In cells homozygous for the Crohn's disease-associated NOD2 frameshift mutation, mutant Nod2 failed to recruit ATG16L1 to the plasma membrane and wrapping of invading bacteria by autophagosomes was impaired. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease.

Combined epicardial and endocardial approach for redo radiofrequency catheter ablation in patients with persistent atrial fibrillation: a randomized clinical trial.

AIMS: An epicardial approach is an effective means to detect and eliminate residual potentials in non-transmural lesions created during prior endocardial ablation. We sought to determine the impact of a combined epicardial and endocardial approach compared with a conventional endocardial approach, on recurrence-free survival after redo ablation. METHODS AND RESULTS: Participants with recurred persistent atrial fibrillation after prior endocardial ablation were randomized (1:1) to undergo treatment with the combined approach (epicardial followed by endocardial ablation) for the treatment group or conventional approach (endocardial ablation only) for the control group. The primary outcome was the time to recurrence of atrial fibrillation or atrial tachycardia following a 90-day blanking period within 12 months after the procedure. The secondary safety outcome was the occurrence of procedure-related complications within 24 h after the procedure. Of 100 randomized participants {median age, 59.0 [(interquartile range (IQR): 53.8-64.3] years, including 16% women, with one prior ablation (IQR: 1-1)}, 93 (93%) completed the trial. Events relevant to the primary outcome occurred in 16 patients in the treatment group and in 21 patients in the control group {Kaplan-Meier estimator percentages, 32 vs. 42%; hazard ratio, 0.71 [95% confidence interval (CI): 0.37-1.37]}. The periprocedural complication rate was lower in the treatment group [2 vs. 16%; odds ratio, 0.11 (95% CI: 0.00-0.87)] with similar achievement of the procedural endpoint in the two groups. CONCLUSION: In the redo procedure for persistent atrial fibrillation, the combined approach had no significant difference of recurrence-free survival and a lower procedural complication rate compared with the conventional approach.

T cell-intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii.

Nod2 belongs to the nucleotide-binding oligomerization domain receptor (NLR) family of proteins, which function as intracellular pathogen sensors in innate immune cells. Nod2 deficiency results in an impaired immune response to bacterial pathogens. However, how this protein promotes host defense against intracellular parasites is unknown. Here we found that Nod2(-/-) mice had less clearance of Toxoplasma gondii and lower interferon-gamma (IFN-gamma) production. Reconstitution of T cell-deficient mice with Nod2(-/-) T cells followed by T. gondii infection demonstrated a T cell-intrinsic defect. Nod2(-/-) CD4(+) T cells had poor helper T cell differentiation, which was associated with impaired production of interleukin 2 (IL-2) and nuclear accumulation of the transcription factor subunit c-Rel. Our data demonstrate a T cell-intrinsic role for Nod2 signaling that is critical for host defense against T. gondii.

Blood flow volume of left atrial appendage measured by magnetic resonance imaging is improved after radiofrequency catheter ablation of atrial fibrillation.

INTRODUCTION: Hemodynamics of left atrial appendage (LAA) is an important factor for future risk of ischemic stroke in atrial fibrillation (AF) patients. Velocity encoded cardiac magnetic resonance imaging (VENC-MRI) can evaluate blood flow volume of LAA without any invasive procedures. We aimed to evaluate the association between radiofrequency catheter ablation (RFCA) and LAA hemodynamics measured by MRI. METHODS AND RESULTS: Consecutive RFCA cases in a single arrhythmia center were retrospectively analyzed. A total of 3120 AF patients who underwent first RFCA were analyzed. Among these patients 360 patients had both pre- and post-RFCA VENC-MRI evaluation. Atrial fibrillation was non-paroxysmal in 174 (48.3%) patients. Mean VENC-MRI (ml/sec) was significantly improved after RFCA with 49.93 ± 32.92 and 72.00 ± 34.82 for pre- and post-RFCA, respectively. Patients with non-paroxysmal AF (∆VENC-MRI = 14.63 ± 40.67 vs. 30.03 ± 35.37; p < .001) and low pre-RFCA VENC-MRI (∆VENC-MRI = 17.19 ± 38.35 vs. 50.35 ± 29.12; p < .001) had significantly higher improvement in VENC-MRI. Those who experienced late recurrence before post-RFCA MRI had significantly less improvement in LAA flow volume (∆VENC-MRI = 15.55 ± 41.41 vs. 26.18 ± 36.77; p = .011). Late recurrence and pre-RFCA VENC-MRI were significantly associated with ∆VENC-MRI after adjusting covariates. Patients who were AF before RFCA but maintained sinus rhythm after RFCA showed greatest improvement in VENC-MRI. CONCLUSION: Effective rhythm control through RFCA can be associated with significant improvement in LAA hemodynamics. Low pre-RFCA VENC-MRI and absence of late recurrence were associated with greater improvement in LAA hemodynamics.

Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon.

Secretory immunoglobulin A (SIgA), the most abundant antibody isotype in the body, maintains a mutual relationship with commensal bacteria and acts as a primary barrier at the mucosal surface. Colonization by commensal bacteria induces an IgA response, at least partly through a T-cell-independent process. However, the mechanism underlying the commensal-bacteria-induced T-cell-independent IgA response has yet to be fully clarified. Here, we show that commensal-bacteria-derived butyrate promotes T-cell-independent IgA class switching recombination (CSR) in the mouse colon. Notably, the butyrate concentration in human stools correlated positively with the amount of IgA. Butyrate up-regulated the production of transforming growth factor ß1 and all-trans retinoic acid by CD103+CD11b+ dendritic cells, both of which are critical for T-cell-independent IgA CSR. This effect was mediated by G-protein-coupled receptor 41 (GPR41/FFA3) and GPR109a/HCA2, and the inhibition of histone deacetylase. The butyrate-induced IgA response reinforced the colonic barrier function, preventing systemic bacterial dissemination under inflammatory conditions. These observations demonstrate that commensal-bacteria-derived butyrate contributes to the maintenance of the gut immune homeostasis by facilitating the T-cell-independent IgA response in the colon.

The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes.

The intracellular sensor Nod2 is activated in response to bacteria, and the impairment of this response is linked to Crohn's disease. However, the function of Nod2 in host defense remains poorly understood. We found that Nod2-/- mice exhibited impaired intestinal clearance of Citrobacter rodentium, an enteric bacterium that models human infection by pathogenic Escherichia coli. The increased bacterial burden was preceded by reduced CCL2 chemokine production, inflammatory monocyte recruitment, and Th1 cell responses in the intestine. Colonic stromal cells, but not epithelial cells or resident CD11b+ phagocytic cells, produced CCL2 in response to C. rodentium in a Nod2-dependent manner. Unlike resident phagocytic cells, inflammatory monocytes produced IL-12, a cytokine that induces adaptive immunity required for pathogen clearance. Adoptive transfer of Ly6C(hi) monocytes restored the clearance of the pathogen in infected Ccr2-/- mice. Thus, Nod2 mediates CCL2-CCR2-dependent recruitment of inflammatory monocytes, which is important in promoting bacterial eradication in the intestine.

Frequent drinking is a more important risk factor for new-onset atrial fibrillation than binge drinking: a nationwide population-based study.

AIMS: Heavy consumption of alcohol is a known risk factor for new-onset atrial fibrillation (AF). We aimed to evaluate the relative importance of frequent drinking vs. binge drinking. METHODS AND RESULTS: A total of 9 776 956 patients without AF who participated in a national health check-up programme were included in the analysis. The influence of drinking frequency (day per week), alcohol consumption per drinking session (grams per session), and alcohol consumption per week were studied. Compared with patients who drink twice per week (reference group), patients who drink once per week showed the lowest risk [hazard ratio (HR) 0.933, 95% confidence interval (CI) 0.916-0.950] and those who drink everyday had the highest risk for new-onset AF (HR 1.412, 95% CI 1.373-1.453), respectively. However, the amount of alcohol intake per drinking session did not present any clear association with new-onset AF. Regardless of whether weekly alcohol intake exceeded 210 g, the frequency of drinking was significantly associated with the risk of new-onset AF. In contrast, when patients were stratified by weekly alcohol intake (210 g per week), those who drink large amounts of alcohol per drinking session showed a lower risk of new-onset AF. CONCLUSION: Frequent drinking and amount of alcohol consumption per week were significant risk factors for new-onset AF, whereas the amount of alcohol consumed per each drinking session was not an independent risk factor. Avoiding the habit of consuming a low but frequent amount of alcohol might therefore be important to prevent AF.

The impact of body weight and diabetes on new-onset atrial fibrillation: a nationwide population based study.

BACKGROUND: Being obese or underweight, and having diabetes are important risk factors for new-onset atrial fibrillation (AF). However, it is unclear whether there is any interaction between body weight and diabetes in regard to development of new-onset AF. We aimed to evaluate the role of body weight status and various stage of diabetes on new-onset AF. METHODS: This was a nationwide population based study using National Health Insurance Service (NHIS) data. A total of 9,797,418 patients who underwent national health check-ups were analyzed. Patients were classified as underweight [body mass index (BMI) < 18.5], normal reference group (18.5 ≤ BMI < 23.0), upper normal (23.0 ≤ BMI < 25.0), overweight (25.0 ≤ BMI < 30.0), or obese (BMI ≥ 30.0) based on BMI. Diabetes were categorized as non-diabetic, impaired fasting glucose (IFG), new-onset diabetes, diabetes < 5 years, and diabetes ≥ 5 years. Primary outcome end point was new-onset AF. New-onset AF was defined as one inpatient or two outpatient records of International Classification of Disease, Tenth Revision (ICD-10) codes in patients without prior AF diagnosis. RESULTS: During 80,130,161 patient*years follow-up, a total of 196,136 new-onset AF occurred. Obese [hazard ration (HR) = 1.327], overweight (HR = 1.123), upper normal (HR = 1.040), and underweight (HR = 1.055) patients showed significantly increased risk of new-onset AF compared to the normal reference group. Gradual escalation in the risk of new-onset AF was observed along with advancing diabetic stage. Body weight status and diabetes were independently associated with new-onset AF and at the same time, had synergistic effects on the risk of new-onset AF with obese diabetic patients having the highest risk (HR = 1.823). CONCLUSIONS: Patients with obesity, overweight, underweight, and diabetes had significantly increased risk of new-onset AF. Body weight status and diabetes had synergistic effects on the risk of new-onset AF. The risk of new-onset AF increased gradually with advancing diabetic stage. This study suggests that maintaining optimal body weight and glucose homeostasis might prevent new-onset AF.

Impact of persistent left superior vena cava on radiofrequency catheter ablation in patients with atrial fibrillation.

AIMS: The impact of persistent left superior vena cava (PLSVC) in atrial fibrillation (AF) patients undergoing radiofrequency catheter ablation (RFCA) is not well known. We performed this analysis to evaluate the electrophysiological characteristics of PLSVC and its role in triggering and maintaining AF. METHODS AND RESULTS: Patients with AF referred to two tertiary hospitals were screened and patients with PLSVC in pre-RFCA imaging studies were enrolled. Among 3967 patients, PLSVC was present in 36 patients (0.9%). There were four morphological types of PLSVC: type 1, atresia of the right superior vena cava (SVC) (n = 2); type 2A, dual SVCs with an anastomosis between right and left SVCs (n = 15); type 2B, dual SVCs without an anastomosis (n = 16); type 3, PLSVC draining into the left atrium (LA; n = 2); and unclassified in one patient. Thirty-two patients underwent RFCA and electrophysiology study focusing on PLSVC: PLSVC was the trigger of AF in 48.4% of patients and the driver of AF in 46.9% of patients. Cumulatively, PLSVC was a trigger or driver of AF in 22 patients (68.8%). Whether to ablate PLSVC was determined by the results of electrophysiology study, and no significant difference in the late recurrence rate was observed between patients who did and did not have either trigger or driver from PLSVC. CONCLUSION: Pre-RFCA cardiac imaging revealed PLSVC in 0.9% of AF patients. This study demonstrated that PLSVC has an important role in initiating and maintaining AF in substantial proportion of patients. Electrophysiology study focusing on PLSVC can help to decide whether to ablate PLSVC.

Comparison between linear and focal ablation of complex fractionated atrial electrograms in patients with non-paroxysmal atrial fibrillation: a prospective randomized trial.

AIMS: Findings regarding efficacy of substrate modification for non-paroxysmal atrial fibrillation (AF) are inconsistent. We prospectively compared clinical outcomes of complex fractionated atrial electrogram (CFAE)-guided focal ablation (CFA) and CFAE-guided linear ablation (CLA) in patients with non-paroxysmal AF. METHODS AND RESULTS: We randomized 150 patients with non-paroxysmal AF into CFA and CLA groups in a 1:1 ratio. Complex fractionated atrial electrogram distribution was evaluated using an automated algorithm of a three-dimensional mapping system. After pulmonary vein isolation (PVI), CFAE-guided ablation was performed in the left atrium and then in the right atrium (RA). When compared with conventional CFA, CLA was performed based on conventional lines, with additional lines. Atrial fibrillation was not induced after PVI alone or with cavotricuspid isthmus ablation in 20.7% of patients. To achieve the endpoint, additional CFAE-guided RA ablation was required in 42.7% and 36.0% of patients undergoing CFA and CLA, respectively (P = 0.403). Atrial fibrillation was terminated during CFAE-guided ablation in 72.9% and 75.0% of patients undergoing CFA and CLA, respectively (P = 0.792). Termination of atrial tachycardia (AT) or non-inducibility of AF/AT was achieved in 61.3% and 68.0% of patients undergoing CFA and CLA, respectively (P = 0.393). The CLA group showed decreased 1-year freedom from AF/AT recurrence (60.0%, CFA vs. 47.3%, CLA; log rank P = 0.085), but no significant difference throughout the follow-up (22.2 ± 21.0 months) (67.1%, CFA vs. 68.9%, CLA; log rank P = 0.298). CONCLUSION: Long-term efficacy of CFAE-guided ablation was unaffected by the ablation technique in patients with non-paroxysmal AF.

Trends in the use of implantable cardioverter-defibrillators for prevention of sudden cardiac arrest: A South Korean nationwide population-based study.

BACKGROUND: The benefits of implantable cardioverter-defibrillators (ICDs) for the prevention of sudden cardiac arrest (SCA) are well established. However, a significant knowledge gap remains regarding current indications and utilization of ICDs in real-world settings in Asia. METHODS: Patients who underwent ICD implantation in South Korea from 2007 to 2015 were identified using the Health Insurance Review and Assessment Service database. We investigated trends in use of ICD for the prevention of SCA. RESULTS: A total of 4649 ICDs were implanted during 9 years. ICDs were implanted in 1448 (31.2%) patients for primary prevention and in 3201 (68.8%) for secondary prevention. The proportion of ICDs for primary prevention increased from 6.1% in 2007 to 41.9% in 2015. Primary prevention was more frequent in older (≥40 years) recipients (34.4% vs. 14.6%, P < .0001). The rates of ICD implantation for primary prevention were highest for nonischemic dilated cardiomyopathy (55.1%) and lowest (9.7%) for inherited primary arrhythmia syndrome (IPAS). CONCLUSION: Our data showed a trend of progressively increasing rates of ICD implantation in Asia, especially for primary prevention of SCA. Primary prevention as an indication for ICD in patients with IPAS remained low.

Characteristics of atrial fibrillation patients suffering atrioesophageal fistula after radiofrequency catheter ablation.

INTRODUCTION: Radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients can cause various complications and atrioesophageal (AE) fistula is one of the most catastrophic complications of RFCA. METHODS AND RESULTS: RFCA registries from 3 cardiovascular centers in the Republic of Korea consisted of 5721 patients undergoing 6724 procedures. Before undergoing RFCA, patients underwent either computed tomography or magnetic resonance imaging. We evaluated clinical, anatomical, and procedural characteristics of patients who developed AE fistula after RFCA. A total of 10 patients developed AE fistula after RFCA (0.15% per procedure). All AE fistulas occurred during first-time RFCA. Eight patients died and mortality rate was 80.0%. No patients had any gastrointestinal symptom at the time of discharge and mean duration time from RFCA to symptom onset was 23.4 days. Six patients (60.0%) had paroxysmal AF. Substrate modification in addition to pulmonary vein isolation was performed in 4 patients (40.0%). Patients with old age, low body weight, and high CHA2 DS2 -VASc score were at increased risk of AE fistula. Baseline imaging evaluation revealed that esophagus had closest contact with LA posterior wall near left inferior pulmonary vein rather than left superior pulmonary vein and all documented AE fistulas were located near left inferior pulmonary vein. CONCLUSION: Posterior wall of LA near left inferior pulmonary vein was the most vulnerable location for AE fistula. Pulmonary vein isolation was the main lesion set associated with AE fistula and old age, low body weight, and high CHA2 DS2 -VASc score were significant risk factors for AE fistula.